Switching from Myrbetriq to Gemtesa for Non-Response
Yes, Gemtesa (vibegron) can and should be tried if a patient does not respond adequately to Myrbetriq (mirabegron), as both are β3-adrenoceptor agonists with similar efficacy profiles but different pharmacologic properties that may result in better response or tolerability. 1
Guideline-Based Rationale for Switching
The AUA/SUFU guidelines explicitly support switching between β3-adrenoceptor agonists when patients experience inadequate symptom control with one medication. 1 The guidelines state that if a patient experiences inadequate symptom control and/or unacceptable adverse drug events with one medication, then a different β3-adrenoceptor agonist may be tried. 1
Clinicians should not abandon β3-agonist therapy if trial of one medication appears to fail or produces an unacceptable adverse event profile. 1
Why Vibegron May Work When Mirabegron Fails
Pharmacologic Differences
Vibegron is a second-generation β3-adrenoceptor agonist that is more potent and highly selective compared to mirabegron. 2, 3
Vibegron does not interact with cytochrome P450 enzymes (CYPs), unlike mirabegron which has significant CYP interactions. 2, 4 This difference may result in better efficacy in patients taking multiple medications that could interfere with mirabegron metabolism. 2
Vibegron demonstrates superior receptor selectivity, which may translate to better efficacy in some patients despite similar class effects. 3
Clinical Efficacy Data
Vibegron 75 mg once daily reduced micturitions by 1.8 episodes per day and urge incontinence episodes by 2.0 episodes per day in the pivotal EMPOWUR trial. 5
Among incontinent patients, vibegron achieved a 75% or greater reduction in urge incontinence episodes in a significantly higher proportion compared to placebo. 5
The 12-week treatment with vibegron demonstrated effectiveness across all OAB symptom variables including urgency, urgency incontinence, and nocturia. 6
Practical Switching Algorithm
Step 1: Define Treatment Failure
- Inadequate symptom control after 4-8 weeks of mirabegron at optimal dose 1
- Unacceptable adverse events (hypertension, drug interactions, cardiovascular effects) 4
- Patient dissatisfaction with symptom improvement 1
Step 2: Switch to Vibegron
- Discontinue mirabegron and initiate vibegron 75 mg once daily with or without food. 7
- No washout period is required given the similar mechanism of action 7
- Tablets should be swallowed whole with water, or may be crushed and mixed with applesauce 7
Step 3: Monitor Response
- Assess symptom improvement at 2,4,8, and 12 weeks using voiding diaries 5
- Monitor blood pressure, especially in patients with pre-existing hypertension 8, 7
- Evaluate for urinary retention, particularly in patients with bladder outlet obstruction or those taking antimuscarinics 7
Safety Considerations When Switching
Cardiovascular Monitoring
- Regular blood pressure monitoring is essential, especially during initial treatment, though vibegron has similar hypertension incidence to placebo (1.7%). 8, 5
- Vibegron is contraindicated in patients with known hypersensitivity to the drug 7
Special Populations
- Use caution in frail elderly patients with mobility deficits, weight loss, weakness, and cognitive deficits, as they may have lower therapeutic index and higher adverse event profiles. 8, 9
- For patients who cannot tolerate pharmacologic management, behavioral strategies including prompted voiding and fluid management should be implemented 8, 9
Urinary Retention Risk
- Monitor for signs and symptoms of urinary retention, particularly in patients with bladder outlet obstruction or those taking muscarinic antagonists concurrently. 7
- Discontinue vibegron if urinary retention develops 7
Combination Therapy Option
If vibegron monotherapy provides partial but insufficient relief after switching from mirabegron:
- Consider adding an antimuscarinic medication (such as oxybutynin) to vibegron, as combination therapy shows superior efficacy compared to monotherapy. 9
- The AUA/SUFU supports combination therapy with a β3-agonist and antimuscarinic for patients who do not respond to monotherapy (Evidence Strength Grade B) 9
- Monitor for additive adverse effects including dry mouth, constipation, and urinary retention when combining medications 9
Common Pitfalls to Avoid
- Do not declare treatment failure with mirabegron until an adequate trial of 4-8 weeks at optimal dose has been completed. 1
- Do not assume all β3-agonists will produce identical responses—pharmacologic differences between mirabegron and vibegron may result in different clinical outcomes. 2, 3
- Do not overlook drug interactions as a cause of mirabegron failure—vibegron's lack of CYP interactions may resolve this issue. 2, 4
- Do not use vibegron in patients with severe uncontrolled hypertension without first optimizing blood pressure control. 8, 7